The present invention provides a composition of a plant material with anti-fatigue activity, its preparation method, usage and related products. The said composition is manufactured from the following plant materials: 20-80% from the genus Rhodiola; 10-60% Gynostemma; 10-60% Lycium. The said composition can be used to manufacture health product, food or anti-fatigue medicine which is able to significantly reduce the fatigue symptoms of those people suffering from fatigue, improve sleeping quality with no impact on normal body physiology. It is shown that the medicine derived from the present invention exerts its anti-fatigue effect through improving the functions of erythrocytes and thrombocytes to enhance the body's ability of supplying oxygen. The medicinal composition of the present invention is characterized by the small effective dose and good water solubility and thus suitable to be made into a variety of dosage forms for use.